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Hepatitis E virus (HEV) is considered responsible for acute hepatitis but has not been thought to cause progression to chronic hepatitis. The authors of this paper identified 14 transplant recipients who had acute HEV infection; in 8, the infection evolved to confirmed chronic hepatitis. The numbers of lymphocytes and of CD2, CD3, and CD4 T cells were significantly lower in the patients with chronic hepatitis than in those in whom the infection resolved. The authors identified 14 transplant recipients who had acute hepatitis E virus infection; in 8, the infection evolved to confirmed chronic hepatitis. The numbers of lymphocytes and of CD2, CD3, and CD4 T cells were significantly lower in the patients with chronic hepatitis. Acute hepatitis caused by the hepatitis E virus (HEV) is endemic in developing countries and appears to be an emerging disease in industrialized countries. 1 , 2 Seroprevalence studies have reported anti-HEV IgG antibodies in 6 to 16% of renal-transplant recipients. 3 , 4 This hepatotropic RNA virus is often not fully considered or routinely sought in cases of acute hepatitis in recipients of solid-organ transplants. Only three cases of acute HEV infection have been reported in organ-transplant recipients. 5 – 7 Even though two cases of persistent HEV infection have been reported, 8 , 9 HEV is considered an agent responsible for acute hepatitis that does not . . .

Depletion of CD4+ T cells from the gut occurs rapidly during acute HIV-1 infection. This has been linked to systemic inflammation and disease progression as a result of translocation of microbial products from the gut lumen into the bloodstream. Combined antiretroviral therapy (cART) substantially restores CD4+ T cell numbers in peripheral blood, but the gut compartment remains largely depleted of such cells for poorly understood reasons. Here, we show that a lack of recruitment of CD4+ T cells to the gut could be involved in the incomplete mucosal immune reconstitution of cART-treated HIV-infected individuals. We investigated the trafficking of CD4+ T cells expressing the gut-homing receptors CCR9 and integrin α4β7 and found that many of these T cells remained in the circulation rather than repopulating the mucosa of the small intestine. This is likely because expression of the CCR9 ligand CCL25 was lower in the small intestine of HIV-infected individuals. The defective gut homing of CCR9+β7+ CD4+ T cells - a population that we found included most gut-homing Th17 cells, which have a critical role in mucosal immune defense - correlated with high plasma concentrations of markers of mucosal damage, microbial translocation, and systemic T cell activation. Our results thus describe alterations in CD4+ T cell homing to the gut that could prevent efficient mucosal immune reconstitution in HIV-infected individuals despite effective cART.

Hepatorenal syndrome (HRS) is a functional renal failure that occurs late during cirrhosis. The prognosis is extremely poor with a mean survival of 1.7 wks from the time of diagnosis. The aim of the present study was to examine the effects of albumin and furosemide administration tailored to central venous pressure (CVP) on renal function and clinical outcome. We treated 20 consecutive patients with HRS. Albumin was given to increase and/or maintain CVP above 3 cm H(2)O. If diuresis remained below 50 mL/h despite effective volume expansion, furosemide was administrated. Patients were considered responders and treatment was discontinued when creatinine clearance rose above 40 mL/min or serum creatinine fell under 132 mumol/L. The need for albumin varied from patient to patient (extremes 40-600 g) and in the same patient from day to day. All but one needed furosemide. Eleven patients (55%) responded to treatment. In this population, diuresis, serum creatinine, and creatinine clearance were all significantly improved. Creatinine clearance at baseline was predictive of treatment efficacy. Survival increased in these patients compared to nonresponders defined as patients with no improvement in renal function (259 days +/- 113 compared to 14 days +/- 3, p < 0.0005). Response to treatment and the type of HRS were the only variables with an independent prognostic value. This study shows that HRS as defined by the International Ascites Club can be treated by albumin administration alone or with furosemide given according to the patient's specific need using CVP.

Hepatitis E virus is a ribonucleic acid (RNA) enterically transmitted virus that causes both epidemics and sporadic cases of acute hepatitis E in many countries of Asia and Africa. Domestically acquired (non-travel-associated) hepatitis E has been reported recently in many industrialized countries including the USA, Europe, and Japan. There is little information available on liver histology in these patients. We report a series of 11 patients with sporadic acute hepatitis E and needle liver histology in South-West France. Hepatitis E was diagnosed based on elevated transaminases (>10 upper limit normal) and the presence of specific serum antibodies (immunoglobulin-G class, present in all 11 patients) and/or viral RNA detection in serum and/or stools. Acute hepatitis lesions were observed in all cases with marked necro-inflammatory activity in nine patients. Confluent necrosis was present in five cases. Anisocaryosis and Kupffer's cell aggregates with siderosis were observed in most of the 11 patients. Cholangitis was frequent (9/11 cases). Cholestasis was observed in eight cases. Pseudo-glandular pattern was present in only one case but without zonal repartition. Characteristic pathological signs of acute hepatitis E were severe intralobular necrosis, polymorph inflammation, and acute cholangitis with numerous neutrophils.

In this randomized trial involving patients with cirrhosis and acute variceal bleeding who were at high risk for treatment failure, control of bleeding was more common and mortality was lower among patients assigned to early treatment with a transjugular intrahepatic portosystemic shunt (TIPS) than among those assigned to standard treatment with rescue TIPS, if needed. In patients with cirrhosis and acute variceal bleeding who were at high risk for treatment failure, control of bleeding was more common and mortality was lower among patients assigned to early treatment with a transjugular intrahepatic portosystemic shunt (TIPS) than among those assigned to standard treatment. Variceal bleeding is a severe complication of portal hypertension and a major cause of death in patients with cirrhosis. Advanced liver failure, failure to control variceal bleeding, early rebleeding, and marked elevations in portal pressure are associated with increased mortality. 1 – 3 Combined treatment with vasoactive drugs, prophylactic antibiotics, and endoscopic techniques is the recommended standard of care for patients with acute variceal bleeding. 4 , 5 However, treatment failure occurs in about 10 to 15% of patients, 6 , 7 who require repeat endoscopic treatments and multiple transfusions. 8 – 10 Treatment with a transjugular intrahepatic portosystemic shunt (TIPS) is highly effective in the control of . . .

The development of pegylated interferons (PEG-IFN) has significantly improved the eradication rates in patients with chronic hepatitis C. Two forms of PEG-IFN have been developed, based on two pegylation chemistries: the 12-kDa linear PEG-IFN-α2b and the 40-kDa branched PEG-IFN-α2a. We compared the in vitro antiviral activity of linear and branched PEG-IFN using the vesicular stomatitis virus (VSV) cytopathic effect (CPE) reduction assay. The specific antiviral activity of branched PEG-IFN was 7% of that of linear PEG-IFN. A given quantity of linear and of branched PEG-IFN does not represent the same biologic activity. A bioassay could give new insights to compare the pharmacokinetic profile of linear PEG-IFN and of branched PEG-IFN.

Pegylated interferon α-2a (Peg-IFN-α) represents a therapeutic alternative to the prolonged use of nucleos(t)ide analog (NA) in chronic hepatitis B (CHB) infection. The mechanisms leading to a positive clinical outcome remain unclear. As immune responses are critical for virus control, we investigated the effects of Peg-IFN-α on both innate and adaptive immunity, and related it to the clinical evolution. The phenotypic and functional features of the dendritic cells (DCs), natural killer (NK) cells and HBV-specific CD4/CD8 T cells were analyzed in HBeAg-negative CHB patients treated for 48-weeks with NA alone or together with Peg-IFN-α, before, during and up to 2-years after therapy. Peg-IFN-α induced an early activation of DCs, a potent expansion of the CD56bright NK subset, and enhanced the activation and functionality of the CD56dim NK subset. Peg-IFN-α triggered an increase in the frequencies of Th1- and Th17-oriented HBV-specific CD4/CD8 T cells. Peg-IFN-α reversed the unresponsiveness of patients to a specific stimulation. Most of the parameters returned to baseline after the stop of Peg-IFN-α therapy. Peg-IFN-α impacts both innate and adaptive immunity, overcoming dysfunctional immune responses in CHB patients. These modulations were not associated with seroconversion, which questioned the benefit of the add-on Peg-IFN-α treatment.

Hepatocellular carcinoma (HCC) is a major public health concern because of the absence of early diagnosis and effective treatments. Efficient diagnosis modalities and therapies to treat HCC are needed. Kruppel-like factor (KLF) family members, such as KLF6, are involved in cell proliferation and differentiation. KLF6 is inactivated in solid tumors, which may contribute to pathogenesis. However, KLF6 status in HCC is controversial. Thus, we undertook the characterization of KLF6 expression and function in HCC and HCC-derived cell lines. We found that HCC, HepG2 and HuH7 cells expressed KLF6 messenger ribonucleic acid and protein. Next, using RNA interference, we demonstrated that inhibiting KLF6 expression in vitro strongly impaired cell proliferation-induced G 1 -phase arrest, inhibited cyclin-dependent kinase 4 and cyclin D1 expression, and subsequent retinoblastoma phosphorylation. Finally, KLF6 silencing caused p53 upregulation and inhibited Bcl-xL expression, to induce cell death by apoptosis. Taken together, these data demonstrated that KLF6 is essential for HCC-derived cells to evade apoptosis.

The ultimate goal of pegylated interferon-alfa-2a (Peg-IFN-α) therapy in chronic hepatitis B (CHB) infection is HBsAg seroconversion. Even though B cells are major mediators of a positive clinical outcome, their modulation during Peg-IFN-α therapy has not yet been described. We investigated here the effects of Peg-IFN-α on eight circulating B-cell subsets thanks to an original multi-gating approach based on CD19, CD27, IgD, CD10, and CD38 markers in patients with CHB treated with nucleos(t)ide analog alone or in combination with Peg-IFN-α. These dynamic changes were analyzed during the 48-weeks of Peg-IFN-α therapy and up to 2 years after the cessation of treatment. The CD19+CD27-IgD+CD10+CD38high transitional B cells and the CD19+CD27+IgD-CD10-CD38high plasmablasts continuously increased, whereas the CD19+CD27-IgD+CD10-CD38low naive, CD19+CD27+IgD+ natural memory, and CD19+CD27+IgD-CD10-CD38low post-germinal center B cells decreased during the course of Peg-IFNα treatment. Such modulations correlated with a sustained increase in sCD30 levels and the decrease in plasma HBsAg. However, no seroconversion occurred and all parameters returned to baseline after the stop of the treatment. Peg-IFN-α therapy mediates a remodeling of B-cell compartmentalization, without clinical relevance. Our study provides new insights into the immunomodulatory effects of Peg-IFN-α on circulating B-cells, and questioned the benefit of the add-on Peg-IFN-α treatment in CHB.